Distribution of glucagon-like peptide-1 and other preproglucagon-derived peptides in the rat hypothalamus and brainstem

Larsen, Philip J.; Tang-Christensen, Mads; Holst, Jens J.; Ørskov, Cathrine

doi:10.1016/s0306-4522(96)00434-4

Cited by 554 publications

(460 citation statements)

References 33 publications

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“…[17][18][19][20][21] GLP-1R ligand is also supplied by proglucagon-expressing neurons of the caudal brainstem that project to GLP-1Rs, which are distributed throughout the brain. [22][23][24] It is interesting to note that stimulation of central GLP-1R results in many of the same responses, for example, inhibition of food intake and increased insulin secretion, as are observed following peripheral ligand injection. It is, however, still unclear whether the central GLP-1 system contributes to the control of energy balance and whether the peripheral and central GLP-1 systems are functionally related.…”

Section: Glp-1mentioning

confidence: 97%

The nucleus tractus solitarius: a portal for visceral afferent signal processing, energy status assessment and integration of their combined effects on food intake

2009

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For humans and animal models alike there is general agreement that the central nervous system processing of gastrointestinal (GI) signals arising from ingested food provides the principal determinant of the size of meals and their frequency. Despite this, relatively few studies are aimed at delineating the brain circuits, neurochemical pathways and intracellular signals that mediate GI-stimulation-induced intake inhibition. Two additional motivations to pursue these circuits and signals have recently arisen. First, the success of gastric-bypass surgery in obesity treatment is highlighting roles for GI signals such as glucagon-like peptide-1 (GLP-1) in intake and energy balance control. Second, accumulating data suggest that the intakereducing effects of leptin may be mediated through an amplification of the intake-inhibitory effects of GI signals. Experiments reviewed show that: (1) the intake-suppressive effects of a peripherally administered GLP-1 receptor agonist is mediated by caudal brainstem neurons and that forebrain-hypothalamic neural processing is not necessary for this effect; (2) a population of medial nucleus tractus solitarius (NTS) neurons that are responsive to gastric distention is also driven by leptin; (3) caudal brainstem-targeted leptin amplifies the food-intake-inhibitory effects of gastric distention and intestinal nutrient stimulation; (4) adenosine monophosphate-activated protein kinase (AMPK) activity in NTS-enriched brain lysates is elevated by food deprivation and reduced by refeeding and (5) the intake-suppressive effect of hindbrain-directed leptin is reversed by elevating hindbrain AMPK activity. Overall, data support the view that the NTS and circuits within the hindbrain mediate the intake inhibition of GI signals, and that the effects of leptin on food intake result from the amplification of GI signal processing.

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Section: Glp-1mentioning

confidence: 97%

The nucleus tractus solitarius: a portal for visceral afferent signal processing, energy status assessment and integration of their combined effects on food intake

2009

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“…For oxytocin, a peptide implicated in ingestive control (136,194), responses obtained with receptor agonists delivered to brainstem or forebrain may be taken to simulate endogenous activation of hypothalamic oxytocinergic neurons. By the same simple logic, ingestive responses obtained from hypothalamic application of glucagon-like peptide (GLP 1 ) (118), another anorexic peptide implicated in the response to leptin (67), arise from receptors normally stimulated by an ascending path from the NTS, the only known source of GLP 1 in the brain (107). Finally, the effects of focal catecholamine and serotonin treatments delivered to hypothalamic sites highlight the functional role of largely (for dopamine), or exclusively, brainstem cell groups (see below).…”

Section: Crh/urocortinmentioning

confidence: 99%

The Neuroanatomical Axis for Control of Energy Balance

Grill

Kaplan

2002

Frontiers in Neuroendocrinology

351

216

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The hypothalamic feeding-center model, articulated in the 1950s, held that the hypothalamus contains the interoceptors sensitive to blood-borne correlates of available or stored fuels as well as the integrative substrates that process metabolic and visceral afferent signals and issue commands to brainstem mechanisms for the production of ingestive behavior. A number of findings reviewed here, however, indicate that sensory and integrative functions are distributed across a central control axis that includes critical substrates in the basal forebrain as well as in the caudal brainstem. First, the interoceptors relevant to energy balance are distributed more widely than had been previously thought, with a prominent brainstem complement of leptin and insulin receptors, glucose-sensing mechanisms, and neuropeptide mediators. The physiological relevance of this multiple representation is suggested by the demonstration that similar behavioral effects can be obtained independently by stimulation of respective forebrain and brainstem subpopulations of the same receptor types (e.g., leptin, CRH, and melanocortin). The classical hypothalamic model is also challenged by the integrative achievements of the chronically maintained, supracollicular decerebrate rat. Decerebrate and neurologically intact rats show similar discriminative responses to taste stimuli and are similarly sensitive to intake-inhibitory feedback from the gut. Thus, the caudal brainstem, in neural isolation from forebrain influence, is sufficient to mediate ingestive responses to a range of visceral afferent signals. The decerebrate rat, however, does not show a hyperphagic response to food deprivation, suggesting that interactions between forebrain and brainstem are necessary for the behavioral response to systemic/ metabolic correlates of deprivation in the neurologically intact rat. At the same time, however, there is evidence suggesting that hypothalamic-neuroendocrine responses to fasting depend on pathways ascending from brainstem. Results reviewed are consistent with a distributionist (as opposed to hierarchical) model for the control of energy balance that emphasizes: (i) control mechanisms endemic to hypothalamus and brainstem that drive their unique effector systems on the basis of local interoceptive, and in the brainstem case, visceral, afferent inputs and (ii) a set of uni-and bidirectional interactions that coordinate adaptive neuroendocrine, autonomic, and behavioral responses to changes in metabolic status. KEY WORDS: feeding behavior; leptin; glucose sensing; decerebrate; neuropeptide; hypothalamic model; caudal brainstem; energy balance.

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“…In addition to an intestinal source (Eissele et al, 1992;Holst, 2007), GLP-1 is produced and released from a group of neurons in the nucleus of the solitary tract (NTS) of the hindbrain (Jin et al, 1988;Larsen et al, 1997). These hindbrain GLP-1 neurons are activated by peripherally administered LiCl (Rinaman, 1999a).…”

Section: Discussionmentioning

confidence: 99%

The Aversive Agent Lithium Chloride Suppresses Phasic Dopamine Release Through Central GLP-1 Receptors

Fortin

Chartoff

Roitman

2015

Neuropsychopharmacol

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Unconditioned rewarding stimuli evoke phasic increases in dopamine concentration in the nucleus accumbens (NAc) while discrete aversive stimuli elicit pauses in dopamine neuron firing and reductions in NAc dopamine concentration. The unconditioned effects of more prolonged aversive states on dopamine release dynamics are not well understood and are investigated here using the malaise-inducing agent lithium chloride (LiCl). We used fast-scan cyclic voltammetry to measure phasic increases in NAc dopamine resulting from electrical stimulation of dopamine cell bodies in the ventral tegmental area (VTA). Systemic LiCl injection reduced electrically evoked dopamine release in the NAc of both anesthetized and awake rats. As some behavioral effects of LiCl appear to be mediated through glucagon-like peptide-1 receptor (GLP-1R) activation, we hypothesized that the suppression of phasic dopamine by LiCl is GLP-1R dependent. Indeed, peripheral pretreatment with the GLP-1R antagonist exendin-9 (Ex-9) potently attenuated the LiCl-induced suppression of dopamine. Pretreatment with Ex-9 did not, however, affect the suppression of phasic dopamine release by the kappa-opioid receptor agonist, salvinorin A, supporting a selective effect of GLP-1R stimulation in LiCl-induced dopamine suppression. By delivering Ex-9 to either the lateral or fourth ventricle, we highlight a population of central GLP-1 receptors rostral to the hindbrain that are involved in the LiClmediated suppression of NAc dopamine release. Neuropsychopharmacology (2016) 41, 906-915;

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Distribution of glucagon-like peptide-1 and other preproglucagon-derived peptides in the rat hypothalamus and brainstem

Cited by 554 publications

References 33 publications

The nucleus tractus solitarius: a portal for visceral afferent signal processing, energy status assessment and integration of their combined effects on food intake

The nucleus tractus solitarius: a portal for visceral afferent signal processing, energy status assessment and integration of their combined effects on food intake

The Neuroanatomical Axis for Control of Energy Balance

The Aversive Agent Lithium Chloride Suppresses Phasic Dopamine Release Through Central GLP-1 Receptors

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